Induced tolerance to cardiac allografts with multiple intravenous injection of donor spleen cells / 中华外科杂志

<p><b>OBJECTIVE</b>To study the methods and mechanisms of immune tolerance in cardiac transplantation.</p><p><b>METHODS</b>Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: untreated, intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat, intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide, 11 days later heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR), the role of interleukin-2 (IL-2) to MLR and the role of tolerant rat splenocytes to MLR were measured after operation.</p><p><b>RESULTS</b>The survival time of heart allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide [MST: (85.3 +/- 7.5) d, t = 0, P < 0.01] was significantly longer than in the groups of untreated [MST: (7.3 +/- 1.0) d], intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat [MST: (7.9 +/- 0.9) d], intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (8.1 +/- 1.2) d], intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (25.8 +/- 3.5) d]. Only a few inflammatory cells infiltrated in cardiac allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide. MLR in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide were significantly decreased compared with those of normal control (t = 0, P < 0.01). IL-2 could partly reversed the hyporesponsiveness of MLR in tolerant rats, the tolerance could be transferred in vitro.</p><p><b>CONCLUSIONS</b>Multiple injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide to recipients could induce immune tolerance to cardiac allografts.</p>

Effect of T suppressor cells on the maintenance phase of tolerance to cardiac allografts in the rats / 中华外科杂志

<p><b>OBJECTIVE</b>To study the role of T suppressor cells in immune tolerance to cardiac allografts in the rats.</p><p><b>METHODS</b>Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: group 1: untreated, group 2: portal venous injection of 3 x 10(8) DA splenocytes to Lewis rat, group 3: intraperitoneal injection of cyclophosphamide (80 mg/kg) to Lewis rat, group 4: portal venous injection of 3 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (80 mg/kg) to Lewis rat, 15 days later heart transplantation was performed. Group 5: intravenous injection 3 (108 splenocytes of group 4 to normal recipient, and then heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR) were measured after operation.</p><p><b>RESULTS</b>The survival time of heart allografts in the group 4 [MST: (71.5 +/- 29.1) d, t = -14.063, -13.915, -13.777; P < 0.01] was significantly longer than in the groups of 1 [MST: (7.3 +/- 1.0) d], 2 [MST: (7.8 +/- 0.8) d], 3 [MST: (8.2 +/- 1.1) d ]. Only a few inflammatory cells infiltrated in cardiac allografts in the groups of 4 and 5. MLR in the groups of 4 and 5 were significantly decreased compared with those of normal control (t = 29.902, 23.047; P < 0.01).</p><p><b>CONCLUSIONS</b>Portal venous injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide could induce immune tolerance to cardiac allografts. The immune tolerance could be transferred through splenocytes. T suppressor cells play an important role in the immune tolerance.</p>

Accelerating hematopoietic recovery in allogeneic bone marrow transplantation mice by co-infusion of marrow stromal cells transduced with dual genes of IL-3/IL-6 / 中国实验血液学杂志

To observe whether bone marrow stromal cell line QXMSC1 (H-2(d)) engineered to secrete IL-3 and IL-6 can improved the hematopoiesis in allogeneic bone marrow transplantation (allo-BMT) mice, the stromal cell line QXMSC1IL-3/IL-6 was established by QXMSC1 cells transduced with the recombined retrovirus vector pL3SN containing mouse IL-3 cDNA and pL6SN containing human IL-6 cDNA. The lethally irradiated C57BL/6 (H-2(b)) mice were engrafted with bone marrow cells (1 x 10(7) cells/mouse BALB/c mice, H-2(d)) in which T cells were depleted by anti-Thy1.2 monoclonal antibody adding complement, and QXMSC1IL-3/IL-6 cells (5 x 10(5)/mouse) were co-infused at same time. The hematopoiesis of recipient mice was observed in 20 and 40 days post-transplantation. Blood RBC and WBC were counted, and nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM were assayed in recipient bone marrow. Results showed that IL-3 and IL-6 were stably expressed in QXMSCQIL-3/IL-6 cells. Compared with BMT and co-infusion with QXMSC1 or QXMSC1 pLXSN cell groups, co-graft with QXMSC1IL-3/IL-6 cells increased the number of blood RBC and WBC in the recipients, and also significantly increased nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM in recipient bone marrow. It is concluded that the marrow stromal cells transduced with IL-3/IL-6 cDNA improve the hematopoiesis in allo-BMT mice. Co-graft with QXMSC1IL-3/IL-6 cells has synergistic effect in accelerating hematopoietic reconstitution.